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Effect of Yersinia pestis YopM on experimental plague
1Department of Microbiology and Immunology, University of Kentucky, Lexington 40536-0084, USA.
Abstract:
YopM of Yersinia pestis has previously been shown to be necessary for full virulence in mice and to be able to bind human alpha-thrombin. This activity prompted the hypothesis that YopM, functioning extracellularly during plague, might be accessible to neutralization by antibody and hence might be a protective antigen. This study tested this hypothesis and found that YopM was not protective, either by passive or active immunization, in inbred or outbred mice. These findings showed that either YopM-specific antibody does not have access to YopM during experimental plague or the function of extracellular YopM is not neutralizable by antibody. Exogenously supplied YopM partially restored virulence to a YopM- strain of Y. pestis while having no effect on lethality of Listeria monocytogenes. These findings indicate that YopM does not significantly alter host defenses important for resistance against heterologous infection (Listeria monocytogenes) but raise the possibility that YopM has a minor extracellular function specific to homologous infection (Y. pestis).
Insights
Yersinia pestis YopM protein, a virulence factor, was not found to be a protective antigen in mice. Antibodies against YopM did not prevent plague, suggesting limited extracellular function or antibody access during infection.
Area of Science:
- Microbiology
- Immunology
- Pathogen-Host Interactions
Background:
- Yersinia pestis YopM is a known virulence factor essential for full pathogenicity in mice.
- YopM's ability to bind human alpha-thrombin suggested potential extracellular function and antibody accessibility.
Purpose of the Study:
- To investigate whether YopM is a protective antigen against Yersinia pestis infection.
- To determine if antibodies against YopM can neutralize its virulence function.
Main Methods:
- Passive and active immunization strategies were employed in inbred and outbred mouse models.
- Virulence restoration assays were performed using a YopM-deficient Y. pestis strain and Listeria monocytogenes.
Main Results:
- YopM immunization (passive or active) did not confer protection against Y. pestis infection in mice.
- Exogenous YopM partially restored virulence to a YopM-deficient Y. pestis strain.
- YopM did not affect lethality in Listeria monocytogenes infections, indicating no significant impact on general host defenses.
Conclusions:
- YopM is not a protective antigen against Yersinia pestis in mouse models.
- Antibody access to or neutralization of extracellular YopM during plague is likely limited.
- YopM may possess a minor, Y. pestis-specific extracellular function, but does not broadly impact host defenses against heterologous pathogens.